A series of phenyl piperidine derivatives possessing potent and selective CCR2 antagonist activity is reported. Structure-activity relationship (SAR) studies have established that incorporation of a second ring system adjacent to the aryl piperidine plays an important role in determining the CCR2 potency. Both a second piperidine ring and a 1,3-substituted cyclopentylamine have been probed as linkers. For the cyclopentylamine series, the 1S,3R-configuration exhibits much higher affinity for hCCR2 than the 1R,3S-configuration. Compound 3g shows good selectivity over CCR1, CCR3, 5-HT and has an excellent P450 profile.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bmcl.2007.07.065 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Serially coupled columns enhance rapid separation and predictive interaction understanding of 93 fentanyl analogs.
Anal Chim Acta
January 2025
College of Pharmacy, Chung-Ang University, 84 Heukseok-ro, Dongjak-gu, Seoul, 06974, Republic of Korea. Electronic address:
Background: The simplicity of synthesis methods has facilitated the illegal manufacture of various fentanyl analogs, leading to numerous fatal overdoses worldwide, particularly in North America. Fentanyl analogs with similar structures are difficult to distinguish due to their fragmentation patterns, making separation using chromatography essential. Additionally, because fentanyl analogs are lethal even in trace amounts, they are easily smuggled, and commonly used fentanyl test strips often fail to detect them due to their low sensitivity.
View Article and Find Full Text PDFCrystal structure and Hirshfeld surface analysis of -(4-nitro-phen-yl)-2-(piperidin-1-yl)acetamide (lidocaine analogue).
Acta Crystallogr E Crystallogr Commun
January 2025
Laboratory of Medicinal Chemistry, Drug Sciences Research Center, Faculty of Medicine and Pharmacy, Mohammed V University, Rabat, Morocco.
In the title mol-ecule, CHNO, the substituents on the phenyl ring are rotated slightly out of the mean plane of the ring but the piperidine moiety is nearly perpendicular to that plane. In the crystal, C-H⋯O hydrogen bonds form chains of mol-ecules extending along the -axis direction, which are linked by C=O⋯π(ring) inter-actions. A Hirshfeld surface analysis showed the majority of inter-molecular inter-actions to be H⋯H contacts while O⋯H/H⋯O contacts are the second most numerous.
View Article and Find Full Text PDFIn vitro metabolism of seven arolyl-derived fentanyl-type new psychoactive substances.
Arch Toxicol
January 2025
School of Chemistry and Chemical Engineering, Guangxi University, Nanning, Guangxi, 530004, People's Republic of China.
Over the past decade, fentanyl-type new psychoactive substances (F-NPS) have emerged as the most representative synthetic opioids in third-generation drugs. These substances are characterized by their "low" fatal dose and parent drug levels in biological matrices, "fast" rates of derivatization and metabolism, and "many" derivatization sites and analogs. The low levels of parent fentanyl NPS in biological matrices complicate their detection, necessitating the use of characteristic metabolites as biomarkers for forensic analysis.
View Article and Find Full Text PDFA Sex-Dependent Cannabinoid CB1 Receptor Role in Circadian Tearing of the Mouse.
Invest Ophthalmol Vis Sci
December 2024
The Gill Institute for Neuroscience, Indiana University, Bloomington, Indiana, United States.
Purpose: We have shown that cannabinoid CB1 receptors regulate both salivation and tearing, but for tearing, this regulation is sex dependent with opposing effects by sex. We investigated a potential interplay of circadian and cannabinoid regulation of tearing.
Methods: We measured cannabinoid and circadian regulation of tearing in CD1 strain mice as well as CB1 receptor protein expression using immunohistochemistry.
Synthesis, anti-urease, molecular docking study and ADMET predictions of piperidine and piperazine Morita-Baylis-Hillman Adducts (MBHAs).
Z Naturforsch C J Biosci
November 2024
Department of Chemistry, COMSATS University Islamabad Campus, 45550, Islamabad, Pakistan.
Article Synopsis
- - The study focuses on creating new heterocycles known as Morita-Baylis-Hillman adducts (MBHAs) using piperidine and piperazine through a Michael addition reaction.
- - Various modifications of the compounds were analyzed through molecular docking and bioactivity studies, revealing their effectiveness against the urease enzyme, with some being significantly potent inhibitors.
- - The compounds showed promising drug-like properties in ADMET predictions, suggesting their potential for further development in medicinal applications.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!